Heart-Stopping News
The diabetes drug Avandia is under fire: What you should know
By Avery Comarow
Posted 5/27/07
Diabetics taking Avandia to control their blood glucose are in a fix. An analysis of 42 studies that was published last week in the New England Journal of Medicine found that for such patients, the risk of heart attack was 43 percent higher than for those not taking the drug. The authors suggested a few possible reasons, such as Avandia’s tendency to raise the level of LDL cholesterol, the bad variety, but made it clear that they didn’t know. U.S. News asked University of Washington internist Bruce Psaty, coauthor of a companion editorial, to help diabetics decipher the findings.

How significant is an increase of 43 percent in heart-attack risk?

The Diabetes Drug Avandia Is Under Fire

It’s a substantially higher risk. Think about it this way-when we use lipid-lowering drugs like statins, we expect to reduce the risk of heart attack by 20 to 40 percent. So there’s as much of an adverse effect from Avandia as there is a beneficial effect from statins.

What if I’m taking this drug?

If you have questions about continuing, you should talk with your doctor about the risks and benefits—don’t try to be your own physician.

What’s your own opinion of Avandia?

I have never prescribed this drug. There was early evidence of weight gain and lipid problems, and it was hard for me to see how this would play out.

Are there other options?

The most effective treatments for diabetes are weight loss and exercise. They improve lipids, blood pressure, and even mood. There are other drugs, and of course there is insulin.

Actos is a similar drug. Is there a reason for those on it to worry?

We need more information. It’s clear that Actos is associated with an increased risk of heart failure. The evidence for increased risk of heart attack doesn’t seem to be there, but to my knowledge, there hasn’t been a complete review of the evidence.

Is there some way to know if I’m one of the patients who might have a problem?

We just know there’s a concern about cardiovascular problems. We lack sufficiently robust information to be able to identify people at higher risk.

Should the Food and Drug Administration take Avandia off the market?

I am not aware of data the FDA and the company may know about. But I don’t know of a reason for physicians to prescribe it.

Reuters Health – May. 28, 2007
NEW YORK (Reuters) – Drug maker GlaxoSmithKline’s medical director said the company’s study of the heart risk associated with its Avandia diabetes treatment may be in jeopardy because patients have dropped out following reports of the drug’s risks, The New York Times reported on Saturday.

Dr. Ronald Krall told the newspaper he did not know how many of the 4,450 patients in the drug trial had withdrawn but said Glaxo diabetes was worried it may not be able to complete the trial, which is scheduled to run through 2008.

‘I was truly frightened on behalf of our patients’
Robin Pagnamenta, Healthcare Industries Correspondent
When he first saw the results of his study two weeks ago, Steven Nissen said that he felt sick and was unable to sleep.

“It was very striking,” he said after the publication of his report on Avandia, the diabetes medicine that is GlaxoSmithKline’s second-bestselling drug. “When you see a signal this strong, I was truly frightened on behalf of our patients.”

The outcome of his “meta-analysis” of 42 clinicial trials was, indeed, troubling. It indicated a 43 per cent increase in the risk of heart attacks and a 64 per cent increase in the risk of death from cardiovascular causes connected to the drug.

“I moved as quickly as humanly possible to publish the data,” Dr Nissen said.

Six days later the publication of his report in The New England Journal of Medicine proved explosive. Within hours, shares in GlaxoSmithKline (GSK) had dropped 8 per cent amid fears that the drug, which generated $3 billion (£1.51 billion) of sales last year and is used by millions, could be pulled or could result in an expensive legal battle.

While GSK, Britain’s biggest pharmaceutical company, and others have strongly attacked the findings, Dr Nissen, cardiology chief of the Cleveland Clinic, Ohio, is not to be dismissed lightly. One of the most respected medical researchers in the United States, he was among the first to find a link between Vioxx, the antiinflammatory drug, and an increased risk of heart attacks.

The scandal that followed forced the drug’s withdrawal in 2004 and thrust Merck, Vioxx’s manufacturer and one of the world’s biggest pharmaceutical companies, into a bruising legal battle that is still continuing.

Dr Nissen made no effort to avoid comparison between Avandia and Vioxx – a parallel that Glaxo has been keen to downplay. “I hope that GSK does not go the same way as Merck did,” he told The Times. “They [GSK] have been marketing a drug with very serious problems. In my view, a lot of people have been harmed.”

When asked for his views on just how many, Dr Nissen pointed to comments made last week by Senator Charles Grassley, an Iowa Republican. He claimed that an evaluation by the US Food and Drug Administration (FDA) had suggested that between 60,000 and 100,000 heart attacks could be linked to the drug since its launch in 1999 – more than 20 per day.

“I feel pretty strongly that our findings are conclusive,” Dr Nissen said. “There is something odd about this drug that increases the risk of cardiovascular problems and death.”

However, GSK is not the only party that disagrees with Dr Nissen.

Many independent experts have raised questions about the small size of the sample used and last week The Lancet, the British medical journal, urged caution about the findings. In an editorial, it gave warning of the dangers of “alarmist headlines and confident declarations that help nobody”.

The FDA has issued a safety alert and is preparing for an Advisory Committee meeting to further analyse the drug.

There is also a political dimension. The FDA has been criticised for being too weak, particularly over its handling of Vioxx and other controversial drugs that have been tied to safety fears. It has come under further pressure from a resurgent Democratic Party in Washington and an American public keen to clip the wings of a pharmaceutical industry that some believe has become too rich and powerful.

Whatever the truth about Avandia’s safety record, confidence in the drug has been undermined. Even JP Garnier, GSK’s chief executive, has admitted that sales in the drug will be affected, although he said last week that they would bounce back once Avandia had been proved to be safe.

Dr Nissen is convinced that his analysis will be vindicated.

“Obviously, there is a lot of pushback,” he said. “This is a commonly used drug that has been taken by many people . . . It’s unfortunate, but this problem is not going to go away.”